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用于具有亚细胞分辨率的神经血管动力学全皮层成像的光声和荧光混合显微镜。

Photoacoustic and fluorescence hybrid microscope for cortex-wide imaging of neurovascular dynamics with subcellular resolution.

作者信息

Liu Liangjian, Xu Zhiqiang, Lai Zhenjie, Xu Bin, Wu Taofeng, Ma Guangying, Zhang Hongdong, Li Jiahao, Ma Weilei, Lei Tiancheng, Li Xiufeng, Guo Zeyi, Song Zheng, Chen Ningbo, Ye Shiwei, Meng Jing, Lai Puxiang, Shen Feng, Chang Junlei, Zhu Yingjie, Zheng Hairong, Zheng Wei, Liu Chengbo

机构信息

Research Center for Biomedical Optics and Molecular Imaging, State Key Laboratory of Biomedical Imaging Science and System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

University of Chinese Academy of Sciences, No. 19(A) Yuquan Road, Shijingshan District, Beijing 100049, China.

出版信息

Sci Adv. 2025 Jul 25;11(30):eadw5275. doi: 10.1126/sciadv.adw5275. Epub 2025 Jul 23.

Abstract

Simultaneously monitoring cortex-wide microvascular dynamics, blood oxygenation metabolism, and neuronal activities with high spatiotemporal resolution is essential for understanding neurovascular coupling (NVC). However, it remains a challenge for existing neuroimaging tools. Here, we report a linear transducer array-based hybrid microscope (LiTA-HM) that integrates photoacoustic microscopy and confocal fluorescence microscopy to achieve simultaneous neurovascular imaging with a field of view (FOV) of 6 millimeters by 5 millimeters, a spatial resolution of ~6 micrometers, and a temporal resolution of 0.8 seconds. We design an array of eight miniature transducers to enlarge FOV and optimize a polygon mirror-based ultrafast scanner to achieve real-time imaging. Proof-of-concept imaging experiments were conducted on awake mice. Different couplings between thousands of neuron somas and vessel branches down to capillaries were observed in hypoxia and anesthesia experiments. Spatiotemporal correlations and functional connectivity in NVC were uncovered for spreading depolarization waves occurred in a drug-induced epilepsy experiment. We expect that LiTA-HM will enable broad applications of neuroimaging.

摘要

以高时空分辨率同时监测全脑皮层微血管动力学、血液氧合代谢和神经元活动对于理解神经血管耦合(NVC)至关重要。然而,这对现有的神经成像工具来说仍是一项挑战。在此,我们报告一种基于线性换能器阵列的混合显微镜(LiTA-HM),它集成了光声显微镜和共聚焦荧光显微镜,以实现视野为6毫米×5毫米、空间分辨率约为6微米、时间分辨率为0.8秒的同步神经血管成像。我们设计了一个由八个微型换能器组成的阵列来扩大视野,并优化了基于多边形镜的超快扫描仪以实现实时成像。在清醒小鼠上进行了概念验证成像实验。在缺氧和麻醉实验中观察到数千个神经元胞体与直至毛细血管的血管分支之间的不同耦合。在药物诱导的癫痫实验中,发现了神经血管耦合中去极化波传播的时空相关性和功能连接性。我们期望LiTA-HM将推动神经成像的广泛应用。

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